Genetic predisposition to alcohol dependence: The combined role of polygenic risk to general psychopathology and to high alcohol consumption.

BACKGROUND: High alcohol consumption and alcohol dependence are only partly genetically correlated and they differ considerably in their correlations with other traits. The existence of genetic correlation among alcohol dependence and psychiatric disorders may be attributed to the presence of a general psychopathology factor, the p factor. This study investigates the relationship of polygenic risk to general psychopathology and to high alcohol consumption on alcohol dependence. METHODS: Participants were 524 alcohol-dependent patients and 729 controls. Polygenic risk scores (PRS) were computed for alcohol consumption (drinks per week) and nine psychiatric disorders. Principal component analysis (PCA) applied to the psychiatric PRS was used to calculate the first principal component as a proxy of the polygenic p factor. RESULTS: Both the polygenic p factor and the drinks per week PRS were associated with alcohol dependence in our sample. Both variables are only weakly correlated, contributing additively to the risk for alcohol dependence. Sensitivity analyses showed that the polygenic p factor was also associated with alcohol dependence in the subset of patients without any psychiatric or substance use comorbidity. CONCLUSIONS: Polygenic risk for alcohol dependence can be split at least into two components, involved in general psychopathology and high alcohol consumption. The first component of PCA based on PRS for different psychiatric disorders allows estimation of the contribution of the polygenic p factor to alcohol dependence. The pleiotropic effects of genetic variants across psychiatric disorders are mainly manifested as alcohol dependence in some patients.

[Caregiver burden and associated factors in family caregivers in the Community of Galicia, Spain]. / Síndrome de carga del cuidador y factores asociados en cuidadores familiares gallegos.

INTRODUCTION: Most of existing work on burden among family caregivers has methodological sample constraints. Moreover, there is contradictory information regarding sociodemographic variables, especially those related to care, clinical variables, and burden. Few studies have analysed the self-esteem and personality characteristics as correlates of burden. In this study, an analysis is performed on the prevalence of burden among family caregivers and the relationship with their sociodemographic, care-related, and clinical characteristics. MATERIALS AND METHODS: The study consisted of a randomly selected sample of 294 family caregivers (mean age 55.3years, 89.8% women) from the Autonomous Region of Galicia, Spain. Trained psychologists assessed the presence of burden via the Zarit Caregiver Burden Interview (CBI). Information was also collected on sociodemographic, care-related variables, social support, personality characteristics, and self-esteem. RESULTS: More than half (55.4%) of the surveyed caregivers exhibited burden (CBI>24), with mean score of 27.3 (SD=13.3). Not being employed outside the home and having higher scores in neuroticism were associated with a greater probability of presenting with burden, while being older and having higher social support were associated with a lower risk. CONCLUSIONS: A significant number of caregivers suffered from burden in the current study. Psychotherapeutic interventions need to be developed for those who are already suffering from burden, as well as prevention strategies for those who have not yet developed it.

Genome wide analysis of rare copy number variations in alcohol abuse or dependence.

Genetics plays an important role in alcohol abuse/dependence. Its heritability has been estimated as 45-65%. Rare copy number variations (CNVs) have been confirmed as relevant genetic factors in other neuropsychiatric disorders, such as autism spectrum disorders, schizophrenia, epilepsy, or Tourette syndrome. In the present study, we analyzed the role of rare CNVs affecting exons of coding genes in a sample from Northwest Spain genotyped using the Illumina Infinium PsychArray Beadchip. After rigorous genotyping quality control procedure, 712 patients with alcohol abuse or dependence and 804 controls were used for CNV detection. CNV calling was performed using PennCNV and cnvPartition, and analyses were restricted to CNVs of at least 100 kb and including at least 10 single nucleotide polymorphisms. Logistic regression was used to test for the effect of CNV as well as number of genes affected by CNVs on case/control status, after adjustment for demographic and experimental covariates. We have found an excess of deletions (p = 0.008) and genes affected by deletions (p = 0.017) in cases. This effect was restricted to the 14.8% of affected genes that are intolerant to loss-of-function mutations (gene count p = 0.009). The importance of this subset of genes is emerging in other psychiatric disorders of neurodevelopmental origin, suggesting that disturbance in neurodevelopment mediated by genetic alterations may be a risk factor for alcohol use disorder.